The major goal of this P01 is to leverage institutional strengths in human, non-human primate, and rodent alcohol research to conduct translafional studies directed at understanding the complex relafionships between eariy life stress and vulnerability to alcohol use disorders. This project will take advantage of a highly producfive and successful translational alcohol research unit at WFHS that was recently established with NIAAA programmatic grant support. This research unit will employ multidisciplinary approaches to identify enduring behavioral and neurobiological consequences of eariy life stress, determine how these alterations contribute to excessive alcohol drinking behaviors, and test novel interventional strategies that may be effective at alleviating addiction vulnerability associated with eariy life stress. The overarching hypothesis is that eariy life stress results in long lasting behavioral alterations that contribute to an increased risk of alcohol addiction (with a focus on anxiety-like behaviors). It is also hypothesized that these behavioral alterations are mediated, in part, by dysregulation of dopamine signaling and glutamate receptor function and plasticity in the nucleus accumbens. Aspects of these hypotheses will be evaluated in human subjects with and without a history of eariy life stress and with well-established non-human primate and rodent models of eariy life stress. This P01 will employ a Center-like structure that will include highly integrated rodent, non-human primate, and human projects. An administrative core will provide the infrastructure and support needed to ensure the success of the research. This core will also actively promote new translational alcohol research through a pilot project program and create new translational research training and outreach activifies related to the scientific goals of the P01. A major emphasis will be to promote scientific integrafion across projects to maximize the likelihood of proceeding from benchside discovery to novel treatment strategies for alcohol addiction. RELEVANCE (See instructions): Relevance of this Research to Public Health: The proposed studies oufiine a multidisciplinary, translational research initiative that will bring together human, non-human primate, and rodent alcohol researchers to address complex and unresolved questions regarding the neurobiological mechanisms that link eariy life stress and alcohol addiction. These translational studies will shed new light on important behavioral phenotypes associated with eariy environmental stress, their association with excessive alcohol drinking, and specific neurobiological mechanisms that may underiie these relationships. This project will also explore novel interventional strategies that may mitigate the increased addicfion vulnerability associated with eariy- life stress. PROJECT/PERFORIViANCE SITE(S) (if additional space is needed, use Project/